Although it is widely recognized that essential trace elements are required for the differentiation, activation and performance of numerous functions of immune cells, the specific roles of these inorganic micronutrients in these processes remain largely undefined. New insights about the participation of zinc, iron and copper in the selection, maturation and early activation events of the immune cells have been gained by judicious use of available tools in analytical cell biology, molecular genetics and array technology. Also, randomly controlled clinical and community trials demonstrate that zinc supplementation can enhance immunocompetence and decrease the incidence and severity of some infections in individuals with diagnosed or suspected mild zinc deficiency. These exciting results provide an impetus to evaluate the potential benefits of supplementation programs for individuals and groups with suboptimal trace element status as a cost-effective means of reducing the risk of infectious diseases.